An extensive pharmacological evaluation of novel anti-nociceptive and IL-6 targeted anti-inflammatory guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li through in-depth in-vitro, ADMET, and molecular docking studies.
An extensive pharmacological evaluation of novel anti-nociceptive and IL-6 targeted anti-inflammatory guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li through in-depth in-vitro, ADMET, and molecular docking studies.
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DOI：
10.1016/j.biopha.2023.114946
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发表时间：
2023-05
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通讯作者：
Ishaq Muhammad;Syed Shams ul Hassan;Wenjun Xu;Guo-li Tu;Hua-Jun Yu;Xue Xiao;Shi‐kai Yan;Huizi Jin;S. Bungău
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文献类型：
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作者：
Ishaq Muhammad;Syed Shams ul Hassan;Wenjun Xu;Guo-li Tu;Hua-Jun Yu;Xue Xiao;Shi‐kai Yan;Huizi Jin;S. Bungău
愈创木烷型倍半萜是肉桂属植物中最常见的倍半萜类化合物，本研究从米告肉桂中分离得到三个新的C-14愈创木烷型倍半萜类化合物和两个新的单萜类化合物，通过现代色谱和波谱技术HRESIMS，1D NMR，2D NMR，实验圆二色性（ECD）和计算圆二色性（ECD）。新型倍半萜类化合物1和2对NO的产生和促炎细胞因子具有显著的抗炎活性。它们对IL-6 mRNA的IC 50值分别测定为9.52和13.42μ M。同样，皮下注射的n-BuT和EA提取物表现出剂量依赖性抑制福尔马林诱导的强直性咬/舔反应在强直性抗伤害性阶段。此外，愈创木烷型倍半萜类化合物1和2的吸收、分布、代谢、排泄和毒性（ADMET）分析显示，这两种化合物均具有高水平的GIT吸收，心脏和肝脏毒性的安全区较高，且对细胞色素无抑制作用。此外，分子对接和模拟研究进一步证实了与IL-6蛋白具有良好结合亲和力的倍半雌酮2的抗炎作用。结果表明，该植物提取物和新分离的愈创木烷型倍半萜类化合物具有较好的生物活性。migaowill提供了新的证据，为传统的使用该物种治疗炎症和伤害感受。
Guaiane-type sesquiterpenoids are most prevalent in the genusCinnamomum.Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated fromCinnamomum migao.The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS,1D NMR,2D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids1and2exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC50values were determined as 9.52 and 13.42μΜagainst IL-6 mRNA, respectively. Similarly, subcutaneous injection ofn-BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids1and2displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene2which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids fromC. migaowill provide new evidence for the traditional use of this species to treat inflammation and nociception.